1bi8
From Proteopedia
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| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bi8 OCA], [http://www.ebi.ac.uk/pdbsum/1bi8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bi8 RCSB]</span> | ||
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[[Category: ink4]] | [[Category: ink4]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:01:33 2008'' |
Revision as of 16:01, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURES CDK6-P19INK4D INHIBITOR COMPLEX
Overview
The cyclin-dependent kinases 4 and 6 (Cdk4/6) that control the G1 phase of the cell cycle and their inhibitor, the p16INK4a tumour suppressor, have a central role in cell proliferation and in tumorigenesis. The structures of Cdk6 bound to p16INK4a and to the related p19INK4d reveal that the INK4 inhibitors bind next to the ATP-binding site of the catalytic cleft, opposite where the activating cyclin subunit binds. They prevent cyclin binding indirectly by causing structural changes that propagate to the cyclin-binding site. The INK4 inhibitors also distort the kinase catalytic cleft and interfere with ATP binding, which explains how they can inhibit the preassembled Cdk4/6-cyclin D complexes as well. Tumour-derived mutations in INK4a and Cdk4 map to interface contacts, solidifying the role of CDK binding and inhibition in the tumour suppressor activity of p16INK4a.
About this Structure
1BI8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a., Russo AA, Tong L, Lee JO, Jeffrey PD, Pavletich NP, Nature. 1998 Sep 17;395(6699):237-43. PMID:9751050
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